Taxol is currently considered a most exciting lead in cancer chemotherapy as it possesses high cytotoxicity and strong antitumor activity. Activity against cisplatin refractory advanced ovarian cancer, as well as activity against breast cancer has been established in the clinic. For the further development of taxol and the development of analogues, several fundamental questions need to be addressed in the future. In this research project, we are addressing one of the issues. We are proposing to conduct structure activity studies concerning the complex diterpene part of the molecule, which has not yet been examined in much detail. Thus, we will systematically probe which functional groups of the diterpene part of taxol are actually necessary for biological activity. This information will be important toward the development of a taxol pharmacophore. These studies will also provide valuable information for the design of novel, potent, second generation taxol derivatives. It is the hope that our studies will allow for the synthesis of less complex taxol analogues which, however, should retain strong cytotoxicity. We are in the unique position that we have 10-deacetyl baccatin III available to us in gram quantities for the proposed studies. 10-Deacetyl baccatin III is not useful as an anticancer agent, but can be chemically converted to taxol or its analogues by a combination of procedures developed in the laboratory of the P.I. and developed by others. Thus no valuable taxol, needed for clinical trials, will be destroyed in this project. Our approach relies on stepwise degradation studies of 10-deacetyl baccatin III, followed by the synthesis of the related C-13 N-benzoyl-3- phenylisoserine derivatives. The C-13 N-benzoyl-3-phenylisoserine side chain of taxol is absolutely required for antitumor activity.